Development of MRI Techniques for Drug-Abuse Applications

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1. Frequency Specificity of Functional Connectivity in Brain Networks Synchronized low-frequency spontaneous fluctuations of the functional MRI (fMRI) signal have been shown to be associated with electroencephalography (EEG) power fluctuations in multiple brain networks within predefined frequency bands. However, it remains unclear whether frequency-specific characteristics exist in the resting-state fMRI signal. In this study, fMRI signals in five functional brain networks (sensorimotor, edefault modef, visual, amygdala, and hippocampus) were decomposed into various frequency bands within a low frequency range (0-0.24 Hz). Results show that the correlations in cortical networks concentrate within ultra-low frequencies (0.01-0.06 Hz) while connections within limbic networks distribute over a wider frequency range (0.01-0.14 Hz), suggesting distinct frequency-specific features in the resting-state fMRI signal within these functional networks. (Neuroimage. 2008 Sep 1;42(3):1047-55) 2. Group Independent Component Analysis Reveals Consistent Resting-State Networks across Multiple Sessions Group independent component analysis (gICA) was performed on resting-state data from 14 healthy subjects scanned on 5 fMRI scan sessions across 16 days. The data were reduced and aggregated in 3 steps using Principal Components Analysis (PCA, within scan, within session and across session) and subjected to gICA procedures. Analyses were performed using all sessions in order to maximize sensitivity and alleviate the problem of component identification across session. Across-session consistency was examined by three methods, all using back-reconstruction of the single session or single subject/session maps from the grand (5 session) maps. The gICA analysis produced 55 spatially independent maps. Biologically relevant component maps were found, including sensory, motor and a 'default-mode' map. All analysis methods showed that components were remarkably consistent across session. Critically, the components with the most obvious physiological relevance were the most consistent. (Brain Research, in press) 3. Mapping spatiotemporal diffusion inside the human brain using a numerical solution of the diffusion equation We demonstrate the feasibility to reveal the spatiotemporal diffusion process inside the human brain based on a numerical solution of the diffusion equation. Normal human subjects were scanned with a diffusion tensor imaging (DTI) technique on a 3-T MRI scanner, and the diffusion tensor in each voxel was calculated from the DTI data. The diffusion equation was discretized into equivalent algebraic equations. A finite-difference method was employed to obtain the numerical solution of the diffusion equation. By specifying boundary and initial conditions, the spatiotemporal evolution of the diffusion process inside the brain can be virtually reconstructed. The proposed method highlights the feasibility to noninvasively estimate the macroscopic diffusive transport time for a molecule in a given region of the brain. (Magn Reson Imaging. 2008 Jun;26(5):694-702) 4. Spectral simplification for resolved glutamate and glutamine measurement using a standard STEAM sequence with optimized timing parameters at various field strengths A spectral simplification approach is introduced that provides unobstructed Glu and Gln measurement using a standard STEAM localization sequence with optimized interpulse timings. The underlying idea is to exploit the dependence of response of a coupled spin system on the echo time (TE) and mixing time (TM) to find an optimum timing set (TE, TM), at which the outer-wings of C4 "pseudo-triplet" proton resonances of Glu and Gln are significantly suppressed while the central peaks are maintained. Density matrix simulation for Glu, Gln, and other overlapping metabolites at 2.3-2.5 ppm was conducted to predict the optimum timing sets. The simulation, phantom, and in vivo results demonstrated that the C4 multiplet proton resonances of Glu and Gln can be resolved for unobstructed detection at 3T, 4T, and 4.7T. (Magn Reson Med. 2008 Feb;59(2):236-44) 5. Synchronized delta oscillations correlate with the resting-state functional MRI signal Electrophysiological recordings and resting-state fMRI measurements were conducted in alpha-chloralose-anesthetized rats. Region-specific, anesthetic dose-dependent fMRI resting-state functional connectivity was detected in bilateral primary somatosensory cortex (S1FL) of the resting brain. Cortical electroencephalographic signals were also recorded from bilateral S1FL; a visual cortex locus served as a control site. Results demonstrate that the resting-state fMRI signal correlates with the power coherence in low-frequency bands, particularly the delta band. These data indicate that hemodynamic fMRI signal differentially registers specific electrical oscillatory frequency band activity, suggesting that fMRI may be able to distinguish the ongoing from the evoked activity of the brain. (Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18265-9) 6. Real-time animal functional magnetic resonance imaging and its application to neuropharmacological studies In the present study, an approach for real-time MRI on a Bruker scanner is presented. The custom software runs on the console computer in parallel with the scanner imaging software, and no additional hardware is required. The utility of this technique is demonstrated in manganese-enhanced MRI (MEMRI) with acute cocaine challenge, in which temporary disruption of the blood-brain barrier (BBB) is a critical step for MEMRI experiments. With the aid of real-time MRI, we were able to assess the outcome of BBB disruption following bolus injection of hyperosmolar mannitol in a near real-time fashion prior to drug administration, improving experimental success rate. (Magn Reson Imaging. In press) 7. Fast T1 mapping technique A fast T1 measurement sequence using inversion recovery Look-Locker echo-planar imaging at a steady state (IR LL-EPI SS) has been developed. Imaging parameters of the the sequence were optimized to minimize the bias from excitation pulse imperfections and to maximize the accuracy and reliability of T1 measurements, which are critical for its applications. Compared to conventional inversion recovery Look-Locker echo-planar imaging (IR LL-EPI) sequence, our new sequence method preserves similar accuracy and reliability, while saving 20% in acquisition time. Optimized IR LL-EPI SS provided quantitative T1 mapping with 114 mm3 resolution and whole brain coverage (28 slices) in approximately 4 minutes. (Magn Reson Med. In review) 8. Metabolic Changes in Rat Frontal Cortex after Injection of Pentylenetetrazole Measured by Proton MR Spectroscopy at 9.4T Seizures were induced in rats by intraperitoneal injection of pentylenetetrazole (PTZ, 70 mg/kg). The time series of metabolite concentrations in the frontal cortex of adult rat brain were measured in vivo before and after the injection by localized 1H MRS spectroscopy at 9.4T (3 time points before the injection and 4 time points after, 25 minutes for each time point). Compared to baseline levels, the average concentrations of glutamine (Gln) and -aminobutyric acid (GABA) (n = 7) significantly increased post injection but reached peaks at different time. 9. Image Registration Technique An implicit reference group image registration algorithm has been developed, which can significantly improve the spatial normalization of a group of images. Assessment of the new technique on anatomical MRI images, diffusion tensor images, and functional MRI showed that this method produces more accurate group-based statistical analysis.